| First Author | Li N | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 1485 |
| PubMed ID | 28469254 | Mgi Jnum | J:275320 |
| Mgi Id | MGI:6296531 | Doi | 10.1038/s41598-017-01411-1 |
| Citation | Li N, et al. (2017) Immune-checkpoint protein VISTA critically regulates the IL-23/IL-17 inflammatory axis. Sci Rep 7(1):1485 |
| abstractText | V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) is an inhibitory immune-checkpoint molecule that suppresses CD4(+) and CD8(+) T cell activation when expressed on antigen-presenting cells. Vsir (-/-) mice developed loss of peripheral tolerance and multi-organ chronic inflammatory phenotypes. Vsir (-/-) CD4(+) and CD8(+) T cells were hyper-responsive towards self- and foreign antigens. Whether or not VISTA regulates innate immunity is unknown. Using a murine model of psoriasis induced by TLR7 agonist imiquimod (IMQ), we show that VISTA deficiency exacerbated psoriasiform inflammation. Enhanced TLR7 signaling in Vsir (-/-) dendritic cells (DCs) led to the hyper-activation of Erk1/2 and Jnk1/2, and augmented the production of IL-23. IL-23, in turn, promoted the expression of IL-17A in both TCRgammadelta(+) T cells and CD4(+) Th17 cells. Furthermore, VISTA regulates the peripheral homeostasis of CD27(-) gammadelta T cells and their activation upon TCR-mediated or cytokine-mediated stimulation. IL-17A-producing CD27(-) gammadelta T cells were expanded in the Vsir (-/-) mice and amplified the inflammatory cascade. In conclusion, this study has demonstrated that VISTA critically regulates the inflammatory responses mediated by DCs and IL-17-producing TCRgammadelta(+) and CD4(+) Th17 T cells following TLR7 stimulation. Our finding provides a rationale for therapeutically enhancing VISTA-mediated pathways to benefit the treatment of autoimmune and inflammatory disorders. |
